The Electrophysiologic Study Of Taurine Magnesium Coordination Compound Resist Arrhythmia Of Cardiac Muscle Cell Induced By Ouabain

Objectives:To investigate the antiarrhythmic mechanism of TMCC,we observed the effect of TMCC on sodium current (INa) and L-type calcium current (ICa,L) in rat ventricular cardiomyocytes of arrhythmia induced by oubaine.Methods:Enzymatic dissociation was used to get single rat ventricular myocytes and whole-cell patch clamp was used to record INa and ICa,L in normal and arrhythmic ventricular cardiomyocytes induced by oubaine in rat exposed to amiodarone and different concentration of TMCC.Results:1. In normal ventricular cardiomyocytes of rat, TMCC (100,200,400μmol·L-1) decreased INa densities from (45.56±1.96) pA/pF to (42.42±4.75) pA/pF, (39.71±1.63) pA/pF, (37.59±4.75) pA/pF (n=5, p<0.01), respectively. The inhibition was in a concentration-dependent manner.24.24μmol·L-1 amiodarone decreased INa densities to (34.23±1.33) pA/pF (n=5,P<0.01). The INa I-V curve was shifted upwards by TMCC and amiodarone without changes of their active, peak and reverse potentials. TMCC and amiodarone turned INa steady-state activation and inactivation curves to right, which made activate and inactivate slowly.2. In arrhythmic ventricular cardiomyocytes of rat induced by 5μmol·L-1 oubaine the INa density decreased from (45.56±1.96)pA/pF to(34.74±1.61) pA/pF(n=5, P<0.01), which was restored to (39.57.42±1.96) pA/pF, (36.61±2.47) pA/pF, (32.95±1.18) pA/pF(n=5,P<0.01) by TMCC (100,200,400μmol·L-1). The the INa density decreased to (28.47±1.65) pA/pF (n=5, P<0.01) by 24.24μmol·L-1 amiodarone. The I-V curve upward shift induced by 5μmol·L-1oubaine was inhibited by TMCC(100,200μmol·L-1) while TMCC(400μmol·L-1)and amiodarone made this shift further. INa steady-state activation and inactivation curve was shifted to the right by 5μmol·L-1 oubaine.3. In normal ventricular cardiomyocytes of rat, TMCC (100,200,400μmol·L-1) changed ICa,L densities from (-4.31±1.62)pA/pF to (4.02±0.75)pA/pF, (4.59±0.30) pA/pF, (5.17±0.20) pA/pF, respectively.400μmol·L-1TMCC increased ICa,L densities significantly (n=5, P<0.01).Amiodarone decreased ICa,L densities to (2.84±0.19) pA/pF (n=5, P<0.01). The ICa,L I-V curve was shifted downwards by 400μmol·L-1TMCC, while upwards by amiodarone.TMCC turned the ICa,L steady-state activation curve to left, while turned inactivation curve to right. Amiodarone turned the Ica,L steady-state activation curve to right, while turned inactivation curve to left..4. In arrhythmic ventricular cardiomyocytes induced by 5μmol·L-1 oubaine the current density decreased from (4.31±1.62) pA/pF to (2.89±0.52) pA/pF, TMCC (100, 200,400μmol·L-1) could inhibit the action of oubaine and made the I-V curve upper shift in a concentration-dependent manner. The ICa,L densities was restored to (2.86±0.65) pA/pF, (3.87±0.57) pA/pF, (4.48±0.91) pA/pF(n=5,P<0.01), respectively.24.24μmol·L-1 amidodarone restored ICa,L densities to (2.55±0.49) pA/pF (n=5, P<0.01).5μmol·L-1 oubaine turned ICa,L steady-state activation curve to right, while inactivation curve to left. TMCC and amiodarone can make them normal.Conclusion:1. TMCC inhibits INa in a concentration-dependent manner in normal cardiomyocytes, meanwhile, TMCC can restore INa to normal in ventricular cardiomyocytes.2. TMCC of lower concentration inhibits ICa,L which TMCC of high concen-tration inhances ICa,L in a biphasic manner in normal myocardiocytes.TMCC restores ICa,L in ventricular myocardiocytes.3. The affection on INa and ICa,L may attribute to the antiarrhythmic effect of TMCC.4. Compared with amiodarone, TMCC is less likely to cause arrhymias.